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categories: ["longevity"]categories: ["longevity"]tags: ["aging", "biomarkers", "measurement", "epigenetics", "frailty"]tags: ["aging", "biomarkers", "measurement", "epigenetics", "frailty"]summary: "An estimate of how far an individual has progressed along the trajectory of age-related decline, expressed in years and compared against their chronological age."summary: "An estimate of how far an individual has progressed along the trajectory of age-related decline, expressed in years and compared against their chronological age."updated: "2026-07-28"updated: "2026-10-29"humanEvidence: "The measures are built and tested in human cohorts, where several predict mortality; none is accepted by a regulator as a surrogate endpoint, and different measures in the same person agree only weakly."humanEvidence: "The measures are built and tested in human cohorts, where several predict mortality; none is accepted by a regulator as a surrogate endpoint, and different measures in the same person agree only weakly."issues: ["The reversal-claims section cites none of the studies whose pattern it describes."]issues: ["The reversal-claims section cites none of the studies whose pattern it describes."]------lines 54–60 → 54–6040 unchanged lines not shown
**Methylation clocks** dominate current research, following the multi-tissue predictor [[steve-horvath]] published in 2013. See [[epigenetic-clock]] for the generations, their training targets, and their reliability problems.**Methylation clocks** dominate current research, following the multi-tissue predictor [[steve-horvath]] published in 2013. See [[epigenetic-clock]] for the generations, their training targets, and their reliability problems. **Deficit accumulation** takes a different route entirely. A frailty index counts the proportion of a long list of health deficits that a person has, without weighting them, and predicts mortality and institutionalisation robustly. It requires no laboratory at all.**Deficit accumulation** takes a different route entirely. A frailty index counts the proportion of a long list of health deficits that a person has, without weighting them, and predicts mortality and institutionalisation reliably. It requires no laboratory at all. **Proteomic measures** read plasma protein levels. Work from Tony Wyss-Coray's laboratory used organ-enriched plasma proteins to estimate the age of individual organs, finding that a substantial fraction of people show one organ aging markedly faster than the rest, with disease risk tracking that organ.[^oh2023] **Immune clocks** built from cytometry and cytokine profiles capture a related axis, linked to [[inflammaging]].**Proteomic measures** read plasma protein levels. Work from Tony Wyss-Coray's laboratory used organ-enriched plasma proteins to estimate the age of individual organs, finding that a substantial fraction of people show one organ aging markedly faster than the rest, with disease risk tracking that organ.[^oh2023] **Immune clocks** built from cytometry and cytokine profiles capture a related axis, linked to [[inflammaging]]. lines 75–81 → 75–8114 unchanged lines not shown
## Reversal claims## Reversal claims Interventions are routinely reported to have "reversed biological age by X years". Almost always the claim rests on a single measure, usually a methylation clock, in a small and often uncontrolled study. The pattern recurs across [[caloric-restriction]] trials, supplement studies, [[metformin]] cohorts and early [[senolytics]] work. Three cautions apply. First, the measure has test-retest variation on the order of the reported effect. Second, a measure trained to predict an outcome is not thereby a cause of that outcome, so moving it need not move the outcome. Third, several of the interventions that shift clock readings, notably [[epigenetic-reprogramming]], act directly on the molecular substrate the clock reads, which makes a clock a particularly poor referee for them.Interventions are routinely reported to have "reversed biological age by X years". The claim almost always rests on a single measure, usually a methylation clock, in a small and often uncontrolled study. The pattern recurs across [[caloric-restriction]] trials, supplement studies, [[metformin]] cohorts and early [[senolytics]] work. Three cautions apply. First, the measure has test-retest variation on the order of the reported effect. Second, a measure trained to predict an outcome is not thereby a cause of that outcome, so moving it need not move the outcome. Third, several of the interventions that shift clock readings, [[epigenetic-reprogramming]] among them, act directly on the molecular substrate the clock reads, which makes a clock a particularly poor referee for them. Regression to the mean compounds the problem in [[consumer-blood-testing|consumer testing]]. A person who tests high, changes their habits and retests will frequently see a lower number regardless of what they did.Regression to the mean compounds the problem in [[consumer-blood-testing|consumer testing]]. A person who tests high, changes their habits and retests will frequently see a lower number regardless of what they did. removed, struck through added, underlinedLine numbers count the serialised markdown of each revision, frontmatter included.
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